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Old antibiotic may find new life as a stroke treatment
Date:5/19/2008

The presence of these enzymes also is a mixed bag. If you want angiogenesis you want to make new blood vessels you need MMPs around to get rid of the old ones, like tearing down an old building to build a new one, says Dr. Hess. However, in patients lucky enough to get the clot buster tPA, the enzyme increases the major risk factor: bleeding. Dr. Hess notes that while this initial clinical trial is in ischemic strokes, he thinks minocycline also may be useful in hemorrhagic strokes, which account for about 12 percent of strokes, where clearly blocking MMPs would come in handy.

Minocycline also works by blocking apoptosis, or cell suicide, an observation originally made by MCG Cell Biologist Zheng Dong. It does this by increasing a protein called bcl-2, which helps cells survive, says Dr. Hess.

The antibiotics potential usefulness in protecting brain cells began surfacing in scientific literature within the last few years. It was so interesting to us because we knew that a lot of the limitations of other drugs that had been tried in rodents but didnt work in stroke patients were that they didnt cross into the brain, Dr. Fagan says. We knew that minocycline did based on previous experiments and the fact that many people who take it for acne or rheumatoid arthritis get dizzy. So we were encouraged by this.

We wanted something we could give at least three hours after stroke or later. In our studies in animal models, we found at delayed time intervals it was profoundly neuroprotective, says Dr. Fagan. We studied it at multiple time points at multiple doses and, in fact, some of the most important work we did was finding out how the rodent dose really could be translated to humans, she says, referencing work published in Experimental Neurology in 2004.

For the clinical trial, Wyeth Pharmaceuticals will make the sterile powder used for injection available from Japan, where its still in use.


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Contact: Toni Baker
tbaker@mcg.edu
706-721-8596
Medical College of Georgia
Source:Eurekalert  

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